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尼罗罗非鱼皮胶原蛋白基质的性能:在创伤愈合的小鼠模型中的初步蛋白质组学研究。

Performance of collagen-based matrices from Nile tilapia skin: A pilot proteomic study in a murine model of wound healing.

机构信息

Keizo Asami Institute (iLIKA), Federal University of Pernambuco (UFPE), Recife, Brazil.

School of Engineering, Mackenzie Presbyterian University, São Paulo, Brazil.

出版信息

J Mass Spectrom. 2024 Jan;59(1):e4988. doi: 10.1002/jms.4988.

DOI:10.1002/jms.4988
PMID:38108530
Abstract

Full-thickness cutaneous trauma, due to the lack of dermis, leads to difficulty in epithelialization by keratinocytes, developing a fibrotic scar, with less elasticity than the original skin, which may have disorders in predisposed individuals, resulting in hypertrophic scar and keloids. Biomedical materials have excellent characteristics, such as good biocompatibility and low immunogenicity, which can temporarily replace traditional materials used as primary dressings. In this work, we developed two dermal matrices based on Nile tilapia collagen, with (M_GAG) and without (M) glycosaminoglycans, using a sugarcane polymer membrane as a matrix support. To assess the molecular mechanisms driving wound healing, we performed qualitative proteomic analysis on the wound bed in an in vivo study involving immunocompetent murine models at 14 and 21 days post-full-thickness skin injury. Gene Ontology and Pathway analysis revealed that both skins were markedly represented by modulation of the immune system, emphasizing controlling the acute inflammation response at 14 and 21 days post-injury. Furthermore, both groups showed significant enrichment of pathways related to RNA and protein metabolism, suggesting an increase in protein synthesis required for tissue repair and proper wound closure. Other pathways, such as keratinization and vitamin D3 metabolism, were also enriched in the groups treated with M matrix. Finally, both matrices improved wound healing in a full post-thick skin lesion. However, our preliminary molecular data reveals that the collagen-mediated healing matrix lacking glycosaminoglycan (M) exhibited a phenotype more favorable to tissue repair, making it more suitable for use before skin grafts.

摘要

全层皮肤创伤,由于缺乏真皮,导致角朊细胞上皮化困难,形成纤维性瘢痕,其弹性比原始皮肤差,在易患个体中可能存在紊乱,导致增生性瘢痕和瘢痕疙瘩。生物医学材料具有良好的生物相容性和低免疫原性等优异特性,可暂时替代传统的初级敷料。在这项工作中,我们使用甘蔗聚合物膜作为基质支持物,开发了两种基于尼罗罗非鱼胶原蛋白的真皮基质,一种具有(M_GAG),另一种没有(M)糖胺聚糖。为了评估驱动伤口愈合的分子机制,我们在涉及免疫功能正常的鼠模型的体内研究中,对 14 天和 21 天全层皮肤损伤后的伤口床进行了定性蛋白质组学分析。基因本体论和途径分析表明,两种皮肤在免疫系统的调节方面都有明显的代表性,强调在损伤后 14 天和 21 天控制急性炎症反应。此外,两组都显示与 RNA 和蛋白质代谢相关的途径显著富集,表明需要增加蛋白质合成以进行组织修复和适当的伤口闭合。其他途径,如角质化和维生素 D3 代谢,在 M 基质处理的组中也有富集。最后,两种基质都改善了全层皮肤病变后的伤口愈合。然而,我们的初步分子数据表明,缺乏糖胺聚糖(M)的胶原介导的愈合基质表现出更有利于组织修复的表型,使其更适合在皮肤移植前使用。

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